Transgenic over-expression of MafK suppresses T cell proliferation and function in vivo

K Yoh1, T Sugawara, H Motohashi

  • 1Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.

Abstract

Insights

Overexpression of MafK in T cells represses gene transcription by binding to MARE-like sequences, impacting T cell proliferation and cytokine production. This highlights MafK

Area of Science:

  • Molecular Biology
  • Immunology
  • Genetics

Background:

  • Small Maf proteins are transcription regulators that bind to Maf recognition elements (MAREs).
  • These proteins lack a transactivation domain, and their transcriptional activity depends on their ratio with partner proteins.
  • The balance of small Maf proteins and partners dictates whether transcription is activated or repressed.

Purpose of the Study:

  • To investigate the role of MafK, a small Maf protein, in T cell transcription.
  • To determine if MafK overexpression represses MARE-dependent transcription in T cells.
  • To assess the impact of MafK on T cell proliferation and cytokine expression.

Main Methods:

  • Generation of transgenic mice overexpressing MafK in the T cell lineage.
  • Analysis of thymocyte counts, IL-2, and IL-4 mRNA expression levels.
  • Electrophoretic gel mobility shift assays (EMSA) to study protein-DNA interactions.

Main Results:

  • MafK overexpression in T cells led to a shortened lifespan due to Pneumocystis carinii pneumonia.
  • Transgenic mice showed decreased thymocytes and reduced IL-2 and IL-4 mRNA levels.
  • EMSA confirmed MafK interaction with IL-2 proximal AP-1 and IL-4 promoter MARE sequences.

Conclusions:

  • Overexpressed MafK represses MARE-dependent transcription by binding to MARE-like sequences.
  • MafK overexpression negatively affects T cell proliferation and cytokine secretion.
  • The MafK homodimer is a valuable tool for studying the role of MAREs in T cell function.